Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas

NCT07694089 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ROID-RAGE-HGG
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to learn whether two alternatives to standard steroid treatment can safely control swelling around a brain tumor after surgery. The study will compare three approaches by placing participants in one of three study groups: standard dexamethasone (a steroid), no routine steroid treatment, and azeliragon, a study drug that may reduce brain swelling through a different pathway. Researchers want to determine whether these alternatives can control swelling while reducing some of the side effects associated with steroid use. Participants in this study will be randomly assigned to one of three study groups. Participants will undergo their planned brain tumor surgery and receive the treatment assigned to their group. Study procedures are the same as their routine care and include physical and neurological examinations, blood tests, MRI scans, review of medical records, and collection of tumor tissue removed during surgery (optional). Most study visits will occur during routine medical care. Participants will be followed for approximately 24 months after surgery.

Conditions

High-grade Gliomas (HGG)

Outcome Measures

Primary Outcomes (1)

• change in peritumoral edema between the preoperative and postoperative period

  The primary outcome is the change in peritumoral edema between the preoperative and postoperative period. Specifically, it is the ratio of postoperative to preoperative peritumoral edema volume, adjusted for extent of enhancing tumor removed. This outcome is derived from MRI-based volumetric assessment and reflects the effectiveness of each perioperative strategy in controlling cerebral edema while accounting for surgical factors

  before the start of adjuvant chemo radiation (up to 6 weeks)

Study Arms (3)

Dexamethasone Arm

ACTIVE COMPARATOR

Standard dexamethasone (steroid) treatment

Drug: Dexamethasone

No-dexamethasone Arm

NO INTERVENTION

No routine dexamethasone treatment

Azeliragon Arm

EXPERIMENTAL

Azeliragon administered for the treatment of brain cancer and to evaluate its capability to control brain swelling around the time of surgery.

Drug: Azeliragon

Interventions

Dexamethasone DRUG

Potent FDA-approved corticosteroid

Dexamethasone Arm

Azeliragon DRUG

orally bioavailable inhibitor of the receptor for advanced glycation endproducts (RAGE)

Azeliragon Arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of screening
• Newly diagnosed supratentorial tumor with imaging characteristics consistent with high-grade glioma
• Candidate for craniotomy with planned resection of more than 50% of the contrast-enhancing tumor
• Midline shift ≤10 mm on preoperative imaging
• Limited pre-enrollment corticosteroid exposure (≤10 mg dexamethasone total and no chronic steroid use within 30 days)
• Karnofsky Performance Status ≥60
• Adequate organ function to undergo surgery and postoperative care as determined by the investigator
• Ability to provide informed consent and comply with study procedures
• Agreement to use effective contraception, when applicable

You may not qualify if:

• Participants meeting any of the following will be excluded:
• Imaging or clinical features highly suggestive of primary CNS lymphoma or metastatic disease
• Posterior fossa tumors or lesions associated with high risk of brainstem compression
• Leptomeningeal or widely disseminated disease
• Clinical conditions requiring immediate corticosteroid therapy
• Prior exposure to high-dose corticosteroids (\>10 mg dexamethasone) or chronic steroid use within 30 days
• Active systemic illness that increases surgical risk, including uncontrolled infection, coagulopathy, or severe cardiopulmonary disease
• Pregnancy or breastfeeding
• Known immunodeficiency or chronic infection requiring immunosuppressive therapy
• Use of investigational agents within 30 days or concurrent use of immunosuppressive medications not permitted by protocol
• Known hypersensitivity to azeliragon
• Inability to undergo MRI due to contraindications such as incompatible implants or severe claustrophobia
• Life expectancy less than 3 months as determined by the investigator
• Participation in another interventional clinical trial prior to initiation of standard adjuvant therapy Vulnerable Populations: This study will not enroll children, pregnant or breastfeeding individuals, or prisoners. Individuals with impaired decision-making capacity may be enrolled only when a legally authorized representative is available to provide consent in accordance with institutional and regulatory requirements.

Sponsors & Collaborators

• Akshitkumar MIstry: lead
• James Graham Brown Cancer Center: collaborator
• Cantex Pharmaceuticals Inc.: collaborator

Study Sites (2)

UofL Health Brown Cancer Center; University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

UofL Health Jewish Hospital

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Interventions

Dexamethasone; azeliragon

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Akshitkumar M Mistry, MD

  UofL Health - Brown Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Akshitkumar M Mistry, MD

CONTACT

502-276-5030; a.mistry@uoflhealth.org

UofL Health Brown Cancer Center

CONTACT

502-562-4370

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Phase II, single-center, randomized, open-label, three-arm parallel-group study

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 9, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Identifiable information will be maintained only as long as necessary for research, regulatory, legal, and record-retention purposes. Until all study activities have been completed.
• Access Criteria: Those who provide funding to the study, outside providers, study safety monitors, government agencies, other sites in the study, data managers, and other agents and contractors used by the study team. Information may also be shared as required by law (for example, to collect or receive information for reporting child abuse or neglect, preventing or controlling disease, injury, or disability, and conducting public health surveillance, investigations or interventions.)

Locations

US (2)